ABSTRACT Support is requested for a Keystone Symposia conference entitled Brain Therapeutics: Disruptive Technologies and Opportunities for Drug Development, organized by Drs. Maria-Jesus Blanco, Kalpana M. Merchant and Mabel Loza Garca. The conference will be held in Santa Fe, New Mexico USA from February 16-19, 2020. CNS disorders represent a major unmet medical need with an associated societal burden that is becoming unsustainable due to changing demographics (e.g., aging population). In response to these burdens, major investments in basic and translational research have been made by government and non-profit institutions world-wide. However, despite these efforts, pharmaceutical companies and equity investors continue to view brain therapeutics as a relatively risky area of investment. This Keystone Symposia conference aims to highlight breakthrough technologies and approaches to de-risk CNS-targeted therapies. More importantly, with the proposed agenda and invited speakers, an aim is to demonstrate how that integration of cross-disciplinary knowledge and approaches has the potential to overcome the contemporary challenges of CNS drug development. One of the unique features of this conference is that it brings together scientists from a range of disciplines, who rarely participate in the same meetings, in order to create an environment that can lead to disruptive innovation. Invited speakers will provide a general overview, as well as in-depth technical presentations, to engage the participants in numerous topics, such as disease biology-informed target selection, novel medicinal chemistry approaches, biomarkers, and clinical trial designs. Advances in technologies such as genomics, imaging and brain delivery will be highlighted throughout. The speakers on the program represent public and private sectors, young and established scientists and world-wide geography. This conference aspires to create an interdisciplinary environment where new collaborations will form that could continue well beyond the conference itself and help address the unmet medical need of CNS disorders. Finally, this meeting is being paired with the Keystone Symposia conference on Cerebral Fluid Flow and Function: Lymphatics, Glymphatics and the Choroid Plexus. The goal of this paring is to stimulate cross-disciplinary thinking about CSF-based medicinal therapies.